Evidence map›Paper›PMID 42420267›Full record

ArticleCell death discovery2026

FOXM1 inhibition primes terminal differentiation of human iPSC-derived hepatocytes.

Kayque Alves Telles-Silva, Lara Pacheco, Sabrina Komatsu, Fernanda Chianca, Gustavo Chagas, Gabrielly Cristine Martins, Maria Gridina, Daria Panchenko, Valdemir Melechco Carvalho, Elia G Caldini and 4 more

Abstract read
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In one paragraph

Article in Cell death discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Kayque Alves Telles-SilvaHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.ORCID http://orcid.org/0000-0002-2994-609X
Lara PachecoHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Sabrina KomatsuHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Fernanda ChiancaHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Gustavo ChagasHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Gabrielly Cristine MartinsDepartment of Hematology and Oncology, Federal University of São Paulo, São Paulo, SP, Brazil.
Maria GridinaThe Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russia.
Daria PanchenkoSirius University for Science and Technology, Sochi, Russia.ORCID http://orcid.org/0009-0003-5911-1231
Valdemir Melechco CarvalhoDivision of Research and Development, Fleury Group, São Paulo, Brazil.
Elia G CaldiniLaboratory of Cellular Biology, Department of Pathology, Medical School, University of São Paulo, São Paulo, SP, Brazil.
Veniamin S FishmanThe Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russia.
Michelle ArkinDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9366-6770
Ernesto GoulartHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Mayana ZatzHuman Genome Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil. mayazatz@usp.br.ORCID http://orcid.org/0000-0003-3970-8025

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human iPSC-derived hepatocytes are widely used in disease modeling. However, late embryonic development in the human liver remains elusive, which hinders differentiation. During late liver embryonic development, Topoisomerase II (TOP2) is downregulated; however, its role in differentiation is unclear. We replicated the TOP2 silencing at birth and identified a transcription factor crucial for hepatocyte differentiation in vitro. Subtoxic inhibition of TOP2 reduces nuclear chromatin condensation without causing DNA damage. RNA-seq analysis revealed that TOP2 inhibition induced cell cycle arrest, accompanied by FOXM1 downregulation. ATAC-seq confirmed that TOP2A inhibition decreased chromatin accessibility and modulated the Wnt/β-catenin pathway. Proteomic analysis demonstrated that FOXM1 inhibition mimicked TOP2A-mediated cell cycle arrest and reduced the levels of fetal hepatocyte proteins. Prolonged FOXM1 inhibition results in increased hepatocyte polyploidization, enhanced CYP450 activity, and improved lipid metabolism. Our findings suggest that FOXM1 inhibition promotes terminal differentiation of human iPSC-derived hepatocytes, potentially paving the way for understanding late embryonic development in the human liver.

Identifiers

PMID42420267

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.